title: Key genes for modulating information flow play a temporal role as breast tumor coexpression networks are dynamically rewired by letrozole.
abstract: BACKGROUND
  Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another.
  
  
  METHODS
  Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial correlation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining network integrity and controlling information-flow.
  
  
  RESULTS
  Letrozole treatment leads to extensive rewiring of the breast tumor coexpression network. Approximately 20% of gene-gene relationships are conserved over time in the presence of letrozole while 80% of relationships are condition dependent. The positions of influence within the networks are transiently held with few genes stably maintaining high centrality scores across the three time points.
  
  
  CONCLUSIONS
  Genes integral for maintaining network integrity and controlling information flow are dynamically changing as the breast tumor coexpression network adapts to perturbation by the drug letrozole.
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth College, HB7937 One Medical Center Dr., Lebanon, NH 03766, USA.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Penrod
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole